Sustained Virological Response Research Articles

Real-life study on the effectiveness and safety of sofosbuvir/velpatasvir-based antiviral agents for HCV eradication in Chinese patients

BackgroundHepatitis C virus (HCV) eradication with Sofosbuvir/velpatasvir (SOF/VEL) represents a significant advancement, offering hope for eliminating the virus in diverse patient populations. But real-world data on its effectiveness and safety remains scarce for patients with chronic hepatitis C (CHC) in China, especially those with HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. MethodsIn this real-world prospective observational study, we recruited patients from West China Hospital and Public Health Clinical Center of Chengdu in China. Patients included adults chronically infected with any HCV genotype, either with or without cirrhosis, HCC, HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection. Patients were administered with SOF/VEL (400/100 mg) ± ribavirin (RBV) once daily for 12 weeks. The primary effectiveness endpoint was sustained virological response at post-treatment Week 12 (SVR12). Adverse events (AEs) were evaluated during treatment. ResultsThe study included 483 patients, with HCV genotypes 1, 2, 3, 6 and uncertain. Among them, 35.4% (171/483, ITT) and 36.7% (166/452, mITT) received SOF/VEL + RBV. At EOT, 99.2% (ITT, 479/483) and 99.1% (mITT, 448/452) of patients had undetectable HCV RNA. The SVR12 rates were 92.8% (ITT, 448/483) and 99.1% (mITT, 448/452). In mITT analysis, the SVR12 for patients infected with HCV GT3b, patients with cirrhosis or HCC, and patients coinfected with HBV/HIV was 99.2% (130/131), 99.4% (168/169), and 97.6% (40/41), respectively. ALBI (-3.01 vs. -3.18 P<0.001), FIB4 (2.53 vs. 1.88, P=0.004) and APRI (0.99 vs. 0.44, P<0.001) showed a significant decrease from baseline to SVR12. None of the involved patients experienced grade 3-5 AEs. ConclusionsAlthough included a high proportion of patients with HCV GT3b, cirrhosis, HCC, or HCV/HBV, HCV/HIV, or HCV/HBV/HIV coinfection, SOF/VEL ± RBV was highly effective and well tolerated in patients with CHC in China.

Evaluation of the clinical and economic value of sofosbuvir/velpatasvir (SOF/VEL) in patients with chronic hepatitis C in Spain during the last 5 years

ObjectiveDirect-acting antivirals for the treatment of hepatitis C virus (HCV) represented a paradigm shift. In 2017, sofosbuvir/velpatasvir (SOF/VEL-Epclusa®) was approved, which showed a high cure rate in all patient, contributing to HCV elimination. The analysis aimed to quantify the clinical and economic value of SOF/VEL in HCV chronic patients since its approval in Spain. MethodsAn economic evaluation was elaborated adapting a Markov model that simulated the lifetime disease progression in of all HCV chronic patients treated with SOF/VEL (30,488 patients) since its launch (5-years), compared to previous therapies. Patients entered the model and were distributed between the fibrosis states (F0-to-F4) in treated and untreated. All patients (100%) were treated with SOF/VEL regardless of their fibrosis, and 49% with previous therapies in ≥F2. The average sustained viral response (SVR) rates 98.9% SOF/VEL versus 61.0% previous therapies. All parameters for the analysis were obtained from real-life data and literature. Only direct healthcare costs associated with disease management were included. The SOF/VEL value was measured as the number of hepatic complications avoided and their associated cost, and hepatic mortality compared to previous therapies. National Health System perspective and a 3% discount rate was applied. ResultsSOF/VEL decreased the number of liver complications, avoiding 92% decompensated cirrhosis, 80% hepatocellular carcinomas, and 87% liver transplants, as well as 85% liver-related mortality. Their cost associated was reduced, amounting to savings of 197M€. ConclusionSOF/VEL adds relevant value to the HCV treatment, reducing the clinical and economic disease burden and contributing to HCV elimination in Spain.

Effectiveness of sofosbuvir-based treatments for patients with hepatitis C virus genotype 6 infection: a real-world study from East China

BackgroundOver the past decade, the proportion of hepatitis C virus (HCV) genotypes (GT) 1 and 2 has decreased in almost all regions of China, while GT 3 and 6 have emerged as new challenges. GT 6 is unique in many respects, like high genetic variability and emerging resistant variants. This study aims to assess the efficacy of sofosbuvir (SOF)-based treatments in patients with GT 6 chronic hepatitis C (CHC).MethodsA retrospective analysis was conducted on patients with GT 6 HCV infection, who were diagnosed between July 2018 and May 2023. All patients received a 12-week course of SOF-based treatments. The primary efficacy endpoint was sustained virologic response (SVR), which is defined as having undetectable HCV RNA at 12 weeks after treatment completion (SVR12). The efficacy data for SVR12 were analyzed using both the evaluated population (EP) and per-protocol population (PP). For the PP populations, efficacy data were stratified using Forrester plots.ResultsA total of 201 patients were included in the study. In PP population, the end of treatment virological response rate was 99.48% (190/191), the SVR12 rate was 99.31% (143/144), and the SVR24 rate was 100.00% (75/75). Only one patient with genotype 6a experienced a relapse 12 weeks after the completion of treatment, but her HCV RNA was undetectable both at the end of treatment and 24 weeks after the end of treatment. Additionally, the normalization rates of alanine transaminase (ALT) and aspartate aminotransferase (AST) were significantly higher at the end of treatment (EOT) compared to baseline (27.36% vs. 93.03%, 36.32% vs. 95.02%, p &amp;lt; 0.001). Significant improvements were observed in the levels of total bilirubin, ALT, AST, albumin, globulin, albumin/globulin ratio, gamma-glutamyl transferase, alkaline phosphatase, platelet, fibrosis-4 (FIB-4), and aspartate transaminase to platelet ratio index (APRI) between baseline and EOT (p &amp;lt; 0.05).ConclusionSOF-based treatments achieved high virological and biochemical response rates in patients with HCV GT 6 infection.

Challenges and Opportunities for Treating Hepatitis C Amongst People Who Use Drugs: Experience of an Integrated Mobile Clinic in Baltimore City.

Progress in treating chronic hepatitis C virus (HCV) infection has been slow amongst people who use drugs (PWUD). This study describes the HCV treatment cascade amongst people accessing a mobile clinic offering integrated low-threshold buprenorphine and infectious disease services in Baltimore City. From May 1, 2021, to December 31, 2022, 560 people had a rapid HCV antibody test, of whom 201 (36%) had a positive result and amongst those, 117 (58%) had an HCV RNA test performed, 81 (40%) had a documented positive RNA, 45 (22%) were prescribed medication, 42 (21%) started medication, 32 (16%) completed medication, 22 (11%) had blood work to assess for sustained virologic response and 20 (10%) had a documented cure. Challenges including housing instability, insurance barriers and lack of venous access limit progress in this cascade. Providing integrated care models to meet the needs of PWUD in the community is necessary but not sufficient to make progress in improving HCV treatment. Removal of insurance restrictions, availability of point-of-care HCV RNA testing, development of rapid HCV treatment guidelines and development of long-acting injectable HCV treatment are needed to move towards a same-day, one-time test and treat model of care.

Histological improvement of fibrosis in patients with hepatitis C who achieved a 5-year sustained virological response to treatment with direct-acting antivirals.

The histological improvement in liver fibrosis in patients with hepatitis C who achieved a sustained virological response (SVR) to direct-acting antiviral (DAA) treatment has not been comprehensively investigated. Therefore, we assessed the histological changes in liver fibrosis among patients with hepatitis C who underwent long-term follow-up after achieving SVR to treatment with DAA. This retrospective study enrolled 71 patients with hepatitis C who achieved SVR to treatment with DAA. Changes in histological liver fibrosis and fibrosis biomarkers (hyaluronic acid, type 4 collagen 7S, Mac-2binding proteinglycosylationisomer, autotaxin, and Fibrosis-4 index) were assessed before and 5years after treatment. Transient elastography using the FibroScan® device was performed 5years after treatment. Advanced fibrosis and cirrhosis were defined as Ishak fibrosis scores of ≥ 4 and ≥ 5, respectively. Histological liver fibrosis significantly regressed after SVR. Fibrosis biomarkers were significantly reduced after SVR. Transient elastography was the most helpful after evaluating the predictive performance of advanced fibrosis and cirrhosis after SVR, with an area under the receiver operating characteristic curve of 0.965 and a cut-off value of 6.75kPa. The cut-off values of serum fibrosis biomarkers for identifying advanced fibrosis and cirrhosis after SVR were lower than those before treatment. Long-term SVR to treatment with DAA ameliorated histological liver fibrosis. Noninvasive tests helped predict the degree of liver fibrosis after SVR, but their cut-off values should be redefined to avoid underestimation of liver fibrosis.

Development and Validation of a PIVKA-II-Based Model for HCC Risk Stratification in Patients With HCV-Related Cirrhosis Successfully Treated With DAA.

Patients with hepatitis C virus (HCV)-related cirrhosis with sustained virological response (SVR) to direct-acting antivirals (DAA) remain at risk of developing hepatocellular carcinoma (HCC). Recently, serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) has shown promising results as an HCC-predictive biomarker. We aimed to develop and validate a PIVKA-II-based model for HCC risk stratification in cirrhotic patients with SVR to DAA. A total of 1220 consecutive patients (Turin, n = 531; Pisa, n = 335; Milan, n = 354) with HCV-related cirrhosis treated with DAA were included in the study. Patients were retrospectively allocated to the training cohort (Turin+Pisa; median follow-up [FU] 39, 22-55 months; incident HCC: 93 [10.7%]) and validation cohort (Milan; median FU 49.0, 35.0-52.0 months; incident HCC: 19 [5.4%]). Serum PIVKA-II levels were measured using the LumipulseG system (Fujirebio, Japan) at SVR12 (Turin and Pisa cohorts) or the end of treatment (Milan cohort). Using Cox regression analysis, a model including PIVKA-II combined with age, sex, ALT, AST, γGT, platelet count, albumin and total bilirubin was derived from the training cohort (C-index = 0.72). In the validation cohort, the model showed a C-index of 0.71 with an area under the curve of 0.84 for identifying patients who developed HCC during the first 12 months of FU. When patients were grouped into three risk categories, the cumulative incidence of HCC was 2.7%, 4.0% and 14.3% in the low-, medium- and high-risk groups, respectively (p < 0.001). Notably, no HCC occurred within 3 years of FU in the low-risk group. Our PIVKA-II-based model showed satisfactory accuracy for HCC risk stratification and may represent a valuable tool for implementing risk-based surveillance protocols in patients with HCV-related cirrhosis with SVR to DAA.

ASO Author Reflections: Impact of Sustained Virological Response After Direct-Acting Antiviral Therapy on Long-Term Outcomes in Patients with HepatitisCVirus-Related Hepatocellular Carcinoma.

ASO Author Reflections: Impact of Sustained Virological Response After Direct-Acting Antiviral Therapy on Long-Term Outcomes in Patients with HepatitisCVirus-Related Hepatocellular Carcinoma.

Effectiveness and Safety of Glecaprevir/Pibrentasvir in Italian Children and Adolescents With Chronic Hepatitis C: A Real-Word, Multicenter Study.

Glecaprevir/Pibrentasvir (GLE/PIB) has been approved by the European Medicine Agency (EMA) and by the US Food and Drug Administration (US-FDA) for the treatment of children and adolescents from 3 years of age with chronic hepatitis C virus (CHC) infection. The aim of this study was to confirm the real-world effectiveness and safety of GLE/PIB in children and adolescents (3 to < 18 years old) with CHC. This prospective, multicentre study involved 11 Italian centres. Children and adolescents (from 3 to < 18 years of age) received a weight-based dose (up to 300/120 mg) of GLE/PIB once daily for 8 weeks. The effectiveness endpoint was sustained virological response 12 weeks after the end of treatment (SVR12). Safety was assessed by adverse events (AE) and clinical/laboratory data. Sixty-one patients (median age 12 years, interquartile range 5) were enrolled and treated between June 2020 and October 2023. Genotype distribution was as follows: 24/61 genotype 1 (39.4%), 13/61 genotype 2 (21.3%), 18/61 genotype 3 (29.5%) and 6/61 genotype 4 (9.8%). Sixty (98.4%) patients completed treatment and follow-up. SVR12 was obtained by 60/61 patients (98.4%). One patient died because of an oncological illness while on treatment. AE occurred in 13.1% of the patients, were mild and no patients prematurely stopped treatment. This study confirmed the real-life effectiveness and safety of the 8-week therapy with GLE/PIB for treatment of CHC in children and adolescents.

Prophylactic 2-week Glecaprevir/Pibrentasvir in Hepatitis C positive to negative kidney transplantation.

Hepatitis C virus (HCV) positive-to-negative kidney transplants (KT) require direct acting antiviral therapy, but the optimal timing and duration remain unclear. We hypothesized that 14-day prophylactic course of glecaprevir/pibrentasvir 300/120mg (GLE/PIB) would be safe and effective at treating donor-derived HCV viremia. This was a prospective, single-center, single-arm, open-label pilot study. 20 adult HCV negative recipients of HCV nucleic acid amplification test positive deceased-donor kidneys (HCV positive-to-negative) received a 14-day course of GLE/PIB, with the first dose pre-transplant. HCV RNA viral loads (VL) were monitored on post-operative days (POD) 1, 3, 7, and 13. If VL was undetectable on POD 13, GLE/PIB was stopped, and if detectable, GLE/PIB was continued to complete an 8-week course. Surveillance monitoring continued after treatment to ensure sustained viral response (SVR). The primary outcome was efficacy of 14-day prophylactic GLE/PIB. Secondary outcomes included patient and allograft survival, the incidence, timing, and clearance of HCV viremia, and safety events. 7/20 subjects (35%) never developed detectable HCV viremia. Only one subject had a detectable, but nonquantifiable, VL on POD 13 and completed an 8-week course. All subjects achieved SVR 12 weeks post-treatment with no relapses through 1-year follow-up. Mean time to undetectable HCV RNA VL was 10.5 (±4.7) days and mean peak VL was 371 (±715) copies/mL. 6-month and 1-year patient and allograft survival were 100% and 95%. A 14-day course of prophylactic GLE/PIB is safe and effective for HCV positive-to-negative KT and may prevent HCV transmission or significantly reduce the VL for those with detectable transmission allowing for rapid clearance within 2 weeks.

Clinical factors to predict changes of esophagogastric varices after sustained viral response with direct-acting antiviral therapy.

The clinical course of esophagogastric varices (EGV) after sustained virological response (SVR) with direct-acting antiviral (DAA) therapy has not been clearly elucidated. The predictors for the worsening/improvement of EGV after SVR with DAA therapy were investigated. Of the cirrhosis patients who achieved SVR with DAA therapy, 328 patients who underwent endoscopic examinations both before and after DAA therapy were enrolled. The predictors of EGV worsening or improvement were investigated. Multivariate analysis identified a history of ascites retention, albumin at baseline, and MELD score at baseline as independent factors that contributed to EGV exacerbation. On multivariate analysis, two factors, BMI and platelet count, were related to EGV improvement. An integrated scoring system was created using these risk factors with or without weighting according to each hazard ratio, and the patients were divided into three groups. A scoring system with weighting of each factor appeared to be more useful, with fewer intermediate patients and more cases classified into the low-risk and high-risk groups. Esophagogastric varices after SVR have a varied clinical course. Using this scoring system that can accurately predict EGV outcomes in clinical settings, it may be feasible to establish a risk-based EGV surveillance plan following SVR.

Externalized nurse-led model for hepatitis C virus microelimination and impact of drug use profile

Background and objectiveDirect-acting antivirals have greatly simplified the treatment of hepatitis C virus (HCV), yet circuits that bring diagnosis and treatment closer to people who inject drugs (PWID) are needed to achieve the elimination targets of the WHO. With this purpose we have established an externalized nurse-driven circuit among former and active PWID in an addiction centre (AC) and a harm reduction centre (HRC). Methods and settingsThe nursing staff offered HCV screening, diagnosis and treatment to the AC and HRC users, administered medication after the hepatologist's remote prescription to those with an active infection who accepted being treated, and implemented educational and harm reduction interventions. Participants and resultsBetween October 2018 and March 2021, 566 users accepted screening. 134 (24%) had an active infection, with a higher prevalence among HRC users (42% vs 17%; p<0.001), who were more frequently foreigners, homeless and reported active drug use and syringe sharing. Treatment initiation was similar between groups. Overall sustained viral response (SVR) for intention-to-treat (ITT) and per protocol (PP) was 70% and 88% respectively. Overall adherence was good in both groups; however, SVR was higher in AC users compared to HRC users (ITT-SVR 81% vs 55%). All reinfections (6% by ITT) occurred in the HRC group. Overall loss to follow-up rate was 21%. ConclusionsThis patient-centred nurse-driven circuit demonstrates that HCV treatment can be successfully delivered to PWID even with active drug use and socio-economic complexity. User-specific characteristics need to be considered when setting up these interventions to maximize success.

Rate of hepatitis C reinfection after successful direct-acting antivirals treatment among people who inject drugs in Spain: the LIVERate study

BackgroundHepatitis C virus (HCV) reinfection following successful treatment threatens the achievement of HCV elimination. The primary aim of this study is to assess reinfection rate three years after sustained virologic response (SVR) in people who inject drugs (PWID) that are on opioid agonist treatment (OAT) who underwent anti-HCV treatment with interferon-free regimens.MethodsObservational, non-interventional, prospective, descriptive study carried out in Spanish tertiary public hospitals between 2017 and 2022. Participants comprised 186 adult HCV infected individuals, 85.5% males with a mean age (Standard Deviation, SD) of 50.1 (5.9). All were enrolled in an OAT program at baseline and had attained SVR 12 weeks after therapy completion with an interferon-free treatment. Baseline data were abstracted from medical chart information collected through the routine clinical practice.ResultsThe overall rate of HCV reinfection three years after SVR12 among PWID was 1.2 new cases per 100 person-years of follow-up at a median of 15.9 months. In the subgroup analyses, those with injection drug practice and without a stable housing had higher reinfection rates.ConclusionAlthough PWID in OAT present a low rate of reinfection by HCV after successful treatment, a closer monitoring in the first year and strengthening inter-consultations with services responsible for monitoring addiction in these patients will be crucial to reduce risky behaviors avoiding HCV reinfection.

Assessment of Glecaprevir/Pibrentasvir Treatment’s Influence on Biochemical and Metabolic Markers in Patients with Chronic Hepatitis

Background/Objectives: Liver function tests (LFT) are essential for diagnosing and monitoring liver status in patients with chronic hepatitis. In addition, tracking the systemic implications reflected in the changes in metabolic parameters is essential for correctly managing the cases. This study addresses the critical gap in the literature by evaluating the effects of glecaprevir/pibrentasvir on key liver function markers (AST, ALT, GGT, TB) and metabolic parameters (TC, TG, HbA1c) in patients with chronic hepatitis C (CHC). Moreover, this study will evaluate the impact of glecaprevir/pibrentasvir on A2MG, which provides insights into its effects on liver fibrosis. Awareness of these effects is critical for the optimal management of patients during and following antiviral therapy to ensure that therapeutic success does not come at the expense of overall liver and metabolic health. These parameters should be monitored as they supply clinicians with essential data, informing treatment more accurately and ensuring a holistic approach in CH patients. Methods: This study consists of 104 patients with chronic hepatitis C treated with glecaprevir/pibrentasvir and monitored from January to June 2024. Assessments comprised standard liver markers, lipid profiles, glycated hemoglobin, and alpha-2-macroglobulin, as well as specific non-invasive tests of liver injury. Results: 95.2% of the patients experienced a sustained virologic response. Biochemical markers and total cholesterol values were significantly decreased with glecaprevir/pibrentasvir therapy. Non-significant elevations in total bilirubin and glycated hemoglobin support the drug’s favorable tolerability profile. Conclusions: In the treatment of chronic hepatitis C patients, glecaprevir/pibrentasvir therapy leads to normalization in biochemical markers (AST, ALT, and GGT), as well as in total cholesterol.

Direct Antivirals Can Achieve a Cure in All Patients With Chronic Hepatitis C due to Genotype 5: A French Multicentre Study.

Hepatitis C virus genotype 5 (HCV-GT-5) is found mainly in South Africa. In our area in central France, the prevalence of HCV-GT-5 is 14%. Here we evaluated sustained virological response at week 12 post-treatment (SVR12) in 147 HCV-GT-5 patients from 14 French university hospitals (2014-2021) treated with direct-acting antivirals (DAA) in real-life. Patients had mainly received sofosbuvir/ledipasvir ± ribavirin, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir. Overall SVR12 was 98% (144/147). Two patients experienced relapse: one was successfully retreated with the same DAAs (sofosbuvir/ledipasvir) plus ribavirin, and the other refused further DAA treatment. One patient with virological failure (sofosbuvir/velpatasvir) had received a second treatment (sofosbuvir/velpatasvir/voxilaprevir) and progressed to cure. HCV-GT-5 patients treated with a DAA regimen had a 99% SVR12 in intention-to-treat (including initial therapy and retreatment) and 100% SVR12 per protocol. Sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and glecaprevir/pibrentasvir show very good efficacy in real-world HCV-GT-5 patients.

Real-life data of hepatitis C treatment with direct acting antiviral therapy in persons injecting drugs or on opioid substitution therapy.

HCV treatment has been revolutionized by introduction of direct-acting antiviral therapy (DAA). Short treatment duration of eight to twelve weeks combined with significantly improved tolerability opened the opportunity to reach out to difficult-to-treat populations. Here, we retrospectively analyzed real life data on HCV treatment adherence and outcome in people who inject drugs (PWID) or on opioid substitution therapy (OST). All PWID or on OST receiving DAA therapy between 3/2021-11/2022 at an infectious disease clinic in Bonn were retrospectively analyzed. Patients received either 8weeks glecaprevir/pibrentasvir or 12weeks sofosbuvir/velpatasvir (+ ribavirin in genotype 3 cirrhotic patients). Sustained virological response (SVR) was measured 4 and 12weeks after HCV therapy. In our cohort 47 patients (68%) received treatment with glecaprevir/pibrentasvir and 22 patients (32%) sofosbuvir/velpatasvir. All 47 (100%) patients started on glecaprevir/pibrentasvir received prescriptions for the full length of therapy, while patients on sofosbuvir/velpatasvir completed 12weeks therapy in 86% and 8weeks in 14% (p = 0.029). Of 69 patients 74% were found to achieve SVR. In 20% no information is available as they were lost to follow-up. Re-infection was documented in 3 patients and one relapse in a gt3 patient with cirrhosis. High adherence and response rates to HCV treatment were found following DAA based therapy in PWID supporting the call to include difficult-to-treat populations into HCV treatment efforts on the way to HCV elimination. Treatment of OST and HCV at one institution supporting patients by a multidisciplinary team may further facilitate adherence to follow up visits enabling documentation of treatment outcomes more easily.

Impact of Sustained Virological Response on Long-Term Outcomes After Curative Resection in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma in the Era of Direct-Acting Antiviral Therapy.

The present study aimed to clarify the long-term outcomes after curative resection of hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients with and without sustained virologic response (SVR) to antiviral therapy. This single-center retrospective cohort study included 216 patients with HCV-related HCC who underwent primary curative resection. Patients were divided into preoperatively achieved SVR, postoperatively achieved SVR through direct-acting antiviral (DAA) therapy and no SVR groups. Associations of SVR and other clinicopathological and surgical variables with overall survival (OS) and recurrence-free survival (RFS) were analyzed. Propensity score (PS) matching was used to reduce selection bias. Patients with pre-SVR (108) and post-SVR (28) had better liver function and less liver fibrosis than those without SVR (80). In multivariate analysis, pre- or post-SVR [hazard ratio (HR), 0.13; 95% confidence interval (CI), 0.03-0.38; P < 0.001] was the only independent predictor of OS. For RFS, pre- or post-SVR (HR, 0.36; 95% CI, 0.18-0.64; P = 0.001) was one of several independent predictors. The study population was divided into the SVR (136 patients) and non-SVR groups. After PS matching, OS and RFS were significantly better in the SVR group (n = 53) than in the non-SVR group (n = 53) (P <0.001 and P = 0.012, respectively). Additionally, OS rates of SVR achieved with DAA were significantly higher than those achieved with interferon (P = 0.019). Achieving SVR by DAA before or after curative resection suppressed recurrence and prevented death in patients with HCV-related HCC.

A precision randomized trial to evaluate the impact of tailored hepatitis C treatment adherence support on HCV treatment outcomes among people who inject drugs in India: Design and Baseline Characteristics of the STOP-C Trial.

Efforts to eliminate hepatitis C virus (HCV) as a public health problem must include people who inject drugs (PWID). We describe the design and baseline characteristics of the Supporting Treatment Outcomes among PWID (STOP-C) trial which evaluates whether HCV treatment outcomes in PWID can be optimized by tailoring treatment support in 7 PWID-focused integrated HIV/HCV prevention/treatment centers. The design is a 3-arm, individual-level precision-randomized trial. Leveraging empirical data, a prediction model assigned participants as minimal or elevated risk for failure. Minimal risk participants were randomized 1:2:3 to low- (basic services), medium- (patient navigation), and high-intensity (patient navigation + directly observed therapy) support, respectively. Elevated risk participants were randomized 3:2:1 to high, medium, and low-intensity support respectively. All received 12 weeks of oral direct-acting antiviral therapy. The primary outcome is sustained virologic response (SVR) 12 weeks after treatment completion in an intention-to-treat analysis. Three thousand participants were randomized (2048 [68%] minimal risk, 952 [32%] elevated risk of failure). This approach will allow for the estimation of efficacy within treatment failure risk strata while preserving the ability to estimate the average treatment effect and has particular relevance with increasing emphasis of precision medicine in health care delivery.

Non-liver malignancies as main cause of mortality after HCV eradication among people living with HIV.

In people living with HIV (PLWH) with HCV infection, liver and non-liver-related mortality significantly decreased after receiving direct acting antivirals (DAAs). We aimed to assess main causes and predictors of mortality after sustained virological response (SVR) induced by DAAs. Retrospective study in antiretroviral treatment-experienced PLWH with HCV infection, followed at San Raffaele Hospital, Milan, Italy, who achieved SVR after DAAs. Kaplan-Meier analysis and log-rank test were used to estimate cumulative probability of death for any cause. Cox proportional hazards model was used to estimate adjusted hazard ratio (aHR) of death and the corresponding 95% confidence interval (95%CI); Baseline variables included in the model were: age, diabetes, hepatocellular carcinoma (HCC), α-fetoprotein (AFP), ALBI grade. Among 663 people included with a median follow-up of 4.4 years (IQR=3.5-5.5), 49 died. Overall 5-year cumulative probability of death was 8.0% (95%CI=5.5%-10.4%); 63.2% (n=31/49) died from non-liver-related events [mainly non-liver malignancies (18/49) and cardiovascular events (7/49)].-. At multivariate analysis, death was more likely in older people [aHR (adjusted Hazard Ratio) (5-year older)=1.46, 95%CI=1.16-1.83, p=0.0009], and in people with diabetes [aHR=2.98, 95%CI=1.55-5.71, p=0.001], ALBI grade ≥2 [aHR=2.13, 95%CI=1.17-3.90, p=0.014] and AFP ≥3.4 ng/mL [aHR=1.96, 95%CI=1.01; 3.84, p=0.049]. In our cohort, non-liver-related events and malignancies were the most common cause of death after HCV eradication. Diabetes, ALBI grade ≥2 and AFP≥ 3.4 ng/L were associated with higher risk of death. In PLWH after HCV eradication, regardless of liver disease stage, surveillance of non-liver events, particularly malignancies, should be recommended.

Long-Term Follow-Up of Neuropsychiatric Symptoms After Sustained Virological Response to Interferon-Free and Interferon-Based Hepatitis C Virus Treatment.

Chronic hepatitis C virus (HCV) infection can be associated with neuropsychiatric symptoms like fatigue and cognitive impairment, independent of the liver status. The present study aims to assess changes in the pattern and extent of neuropsychological symptoms after successful treatment with interferon (IFN)-based and IFN-free therapy. HCV-infected patients who underwent neuropsychological assessment in previous studies were invited to a follow-up examination. Patients were grouped according to the treatment status: Sustained virological response (SVR) after IFN treatment (IFN SVR, n = 14) or after therapy with direct acting antivirals (DAA SVR, n = 28) or ongoing HCV infection (HCV RNA+, n = 11). A group of 33 healthy controls served as reference. Patients completed self-report questionnaires addressing health-related quality of life (HRQoL), mood and sleep quality and a neuropsychological test battery including tests of memory and attention (Luria's list of words, PSE test, cancelling "d" test, Word-Figure-Memory Test and computer-based test battery for the assessment of attention [TAP]). At baseline, all three patient groups had worse fatigue, depression, anxiety and HRQoL scores compared to healthy controls. Longitudinal analysis revealed that fatigue and mood slightly improved in all patient groups over time, while HRQoL improved in SVR patients but not in HCV RNA+ patients. Memory test results improved significantly in all patient groups, irrespective of their virological status. In contrast, the attention test results showed no clear change from baseline to follow-up. Our data can be considered as a hint that HCV eradication-independent of therapy regimen-does not substantially ameliorate neuropsychiatric symptoms in HCV-afflicted patients.

The effect of cognitive emotion regulation on direct-acting antivirals adherence in patients with hepatitis C.

Adherence to direct-acting antivirals (DAAs) could be a predictor of chronic viral hepatitis C (HCV) therapeutic failure. We examined the perceptions of patients receiving DAAs to determine how cognitive factors influence their decision to maintain adherence. Also, we explored the threshold of DAAs adherence for obtaining sustained virologic response (SVR) among patients with HCV, in order to better implement a strategy that improves the DAAs adherence in the future clinical practice. A single-arm prospective study was performed. Patients with HCV that started and completed DAAs treatment in the County Hospital of Craiova, Dolj, Romania, were enrolled. Patients' medication adherence was assessed using the HCV-AD10 questionnaire, and the cognitive emotion regulation was measured with CERQ questionnaire (five positive/adaptive cognitive emotion-regulation domains and four negative/maladaptive domains). Spearman correlation analysis was conducted to explore the relationships between adherence and different factors. ROC-curves were used to evaluate the adherence threshold to achieve SVR. A linear regression model was performed to analyze the primary outcome (DAAs adherence) to be the target variable based on given independent variables (age, treatment duration, severity of HCV, the nine adaptive and maladaptive strategies). 368 patients (mean age: 61years) with HCV diagnosed 4.05 ± 6.38 (average) years ago were enrolled. Mean (±SD) adherence via HCV-AD10 was 91.51 ± 8.34, and the proportion of the participants achieving SVR was 96%. Patients with an adherence less than 84% (5 patients, 1.36%) was considered nonadherent and they have a high probability of not achieving response (sensitivity and specificity of 83% and 80%, respectively). We obtained significantly higher values of three adaptive strategies between adherent and nonadherent patients following DAAs treatment: in positive refocusing (p-value = 0.044), refocus on planning (p-value = 0.037), and positive reappraisal (p-value = 0.047). The interplay between the three adaptive strategies of the cognitive emotion regulation and the enhancement of DAAs adherence contributes to a more holistic comprehension of patient behavior in the context of HCV treatment. Increasing refocusing and planning using goal setting and assisting patients in establishing specific, achievable goals can be crucial strategies for clinicians aiming to improve adherence among their patients.